Rapid onset synovial inflammation and hyperplasia induced by transforming growth factor beta.
After intraarticular injection of TGF-beta 1 or TGF-beta 2, marked swelling and erythema of the injected joints were apparent within 12-24 h. On a scale of 0 to 4, by day 3, the TGF-beta-treated joints had articular indices (AI) of 3.6 +/- 0.5 to 4.0 +/- 0.0 compared with no response for the vehicle-injected contralateral joints. Histopathologic evaluation revealed a predominantly mononuclear phagocyte infiltrate with some neutrophils and T lymphocytes, consistent with active inflammation. The monocytic pattern of leukocyte infiltration at 2-3 d was comparable to that seen in animals with antigen-induced arthritis after 2-3 wk. Extensive synovial fibroblast hyperplasia became apparent within 48 h, likely as a result of TGF-beta induction of growth factor synthesis by the accumulating monocytes. TGF-beta 2, a homologue of TGF-beta 1, was found to induce a similar level of synovitis and synovial hyperplasia consistent with its parallel monocyte and fibroblast chemotactic properties and ability to induce transcription and translation of monocyte/macrophage-derived growth factors. These data suggest that TGF-beta, released by platelets and activated inflammatory cells, may play a direct role in leukocyte recruitment and activation in arthritic and other chronic inflammatory lesions.
Allen
J B
JB
Cellular Immunology Section, National Institute of Dental Research, Bethesda, Maryland 20892.
Manthey
C L
CL
Hand
A R
AR
Ohura
K
K
Ellingsworth
L
L
Wahl
S M
SM
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D006965:Hyperplasia; D007249:Inflammation; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D008854:Microscopy, Electron; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000633:toxicity; D012016:Reference Values; D013583:Synovial Membrane / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D015291:Transforming Growth Factors / Q000633:toxicity*
D011994:Recombinant Proteins; D015291:Transforming Growth Factors